LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease

Abstract

IntroductionThe long non-coding RNA Brain-derived nutritional factor anti-sense RNA (BDNF-AS) is a type of anti-sense RNA that has been proven to play a crucial role in the occurrence and development of certain nervous system disorders. However, the role and molecular mechanism of BDNF-AS in Alzheimer's disease (AD) have not been elucidated yet. MethodsPeripheral blood samples were collected from outpatients with AD as well as from normal elderly individuals in the community, and the expression of BDNF-AS was analysed using quantitative reverse transcription-polymerase chain reaction. An in vitro model was constructed, and the effect of BDNF-AS expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of BDNF-AS in AD was examined using the luciferase reporter, MS2-RIP, and RNA pulldown assays. ResultWe found that the expression of BDNF-AS was elevated in the peripheral blood of patients with AD and that increased BDNF-AS expression may be associated with the cognitive status of such patients. The results confirmed that BDNF-AS could promote neurotoxicity in the in vitro model. Then, we uncovered that BDNF-AS promotes the expression of BACE1 through the competitive binding of miR-9-5p, thereby promoting amyloid deposition. Finally, through the Morris water maze, we found that the high expression of BDNF-AS promoted cognitive impairment in AD mice. ConclusionThe obtained results suggest that BDNF-AS plays a crucial role in the occurrence and development of AD. As a new pathogenic gene of AD, BDNF-AS may be used as a therapeutic target or as a prognostic marker in patients with AD.